We investigated the alterations of phospholipase C activity in the kidney and arterial wall of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Neither DOCA nor salt administration alone affected phospholipase C activity in the kidney and arterial wall. In contrast, when the rats were given both DOCA and salt and developed high blood pressure, the phospholipase C activity became greater in the outer and inner medulla (papilla) while the enzyme activity was reduced significantly in the renal cortex and arterial wall. Such an increase in phospholipase C activity was not observed in the kidney of a genetic rat for spontaneous hypertension. Moreover, the phospholipase A2 activity was also stimulated in the renal medulla of DOCA-salt hypertensive rats. Thus, these data indicate that DOCA-salt hypertension is associated with an increase in phospholipase C activity in the renal medulla, which seems primary to the development of DOCA-salt hypertension.